5613426 LOW CHRONIC INFLAMMATION IN SCD
Authors: M.R. Rolli, D.V. Venturelli
Journal: HemaSphere (2023)

Introduction: Sickle Cell Disease (SCD) is a genetic disorder of hemoglobin affecting 30 million people worldwide in which the mutant HbS polymerize upon deoxygenation, causing the eritrocyte to assume a sickle morphology and reduce the fluidity of cell membrane, adhering to leucocyte immobilized to the endothelium, causing microvascular occlusion, vaso occlusive crisis and tissue ischemia (1). In additon to eritrocyte sickling, one of the hallmarks of SCD is the continuous presence of basal inflammatory process. SC patients report the following condition: higher baseline leucocyte count (2) Higher level of soluble CD62L (3) neutrofils express higher activation molecules, CD64 (4), CD11b/CD18 (5) monocytes demonstrate activated phenotypes and higer propensity to IL-1beta and TNF-alfa (6) platelets are chronically activated and express higher level of CD40L (7) patience exhibit increased intestinal permeability related to enterocyte injury (8) gut disbiosis that is associated with hospitalization and VOC (9) Ongoing inflammatory process not only render SCD patience to developing VOC, they also create vicious cicle of the pathology that represent a significant risk in the progression of the disease and in chronic damage tissue. Aims: While advance have been made to reduce the frequency of VOC in SCD, there have been very little change in the management of patience during symptom-free “steady state”. The results from various studies on treating VOC using monotherapy have so far been universally disappointing. This is not surprising in view of the complex nature of VOC. Successful treatment of VOC targeting of the downstream immunological pathways requires multipronged approaches using combination therapy, just like treatment of malignant diseases using combination chemotherapy. Methods: The reviwes of the scientific litterature is full of interesting articles in which is enlighted the interaction between the immune system and different stimuli in order to obtain a modulation of the immune reasponse toward a tolerogenic way. Results: In PubMed there are very interesting report that investigate the approach to the immune system in SCD in order to reduce the basal inflammation. There are many way to interact with the immune system to promote a tolerogenic way in SCD such as: supplement of Vitamin D to reduce resporatory illness (10) supplement of Omega-3 to reduce CRP (11) supplement of Glutamine to reduce hospitalization and pain crises (12) probiotic or enterosorbent can reduce gut disbiosis and ameliorate clinical outcome (13) moderate exercise improve cardiopulmonary function and quality life (14) (15) Conclusion: SCD is a genetic disorder caracterized by a continuous presence of low chronic inflammation and studies in human have found that in SCD patience, the more the immune system is activated, the more are likely to get involved in clinical complication such alloimmunization, hospitalization and pain crises (16). Recent evidence suggest that bioregulatory approach toward a tolerogenic way of the immune response could lead to an amelioration of clinical outcome and improvement of quality of life with cheap and feasible approaches. References 1. Centers for Disease Control and Prevention. 2020. Data and statistics on sickle cell disease. www.cdc.gov/ncbddd/sicklecell/data.html 2. Anyaegbu CC et al, Eur J Haematol. 1998;60:267–268. 3. Dutta D et al, J Transl Med. 2019;17:183. 4. Lard LR et al, J Leukoc Biol. 1999;66:411–415. 5. Lum AF et al, Am J Hematol. 2004;76:126–133. 6. Belcher JD et al, Blood. 2000;96:2451–2459. 7. Sparkenbaugh E et al, Br J Haematol. 2013;162:3–14. 8. Dutta, D et al, J Transl Med 17, 183 (2019). 67-019-1938-8 9. Dutta D et al, Br J Haematol. 2020 Feb;188(4):488-493. 10. Lee MT et al, Blood Adv. 2018 May 8;2(9):969-978. 11. Setty BNY et al, Prostaglandins Leukot Essent Fatty Acids. 2019 Jul;146:11-18. 12. Niihara Y et al N Engl J Med. 2018 Jul 19;379(3):226-235. 13. Dutta D et al, Br J Haematol. 2020 Feb;188(4):488-493. 14. Gellen B et al, Lancet Haematol. 2018 Nov;5(11):e554-e562. 15. de Araujo Junior JA et al, PLoS One. 2021 May 12;16(5):e0250128. 16. Hendrickson JE, et at, Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):446-451.